The Women's Health and Functional Visceral Disorders Center is composed of a cohesive group of clinical investigators and basic scientists with strong independent grant-supported research programs in the interactions between the nervous system and the viscera, with special emphasis on stress neurobiology, sex differences and chronic functional disorders. The main focus of the Center is the identification of sex-related factors that play a role in the development, clinical manifestation and treatment response of two common visceral pain syndromes, e.g. Irritable Bowel Syndrome (IBS) and Interstitial Cysitits (iC). Both disorders are common, occur more commonly in females, appear to show sex differences in treatment reponses and cause signficant morbidity and impairment in quality of life. The Center has two clinical and two basic science Projects, which closely interdigitate and overlap in terms of thematic, experimental approach and hypotheses. Thus, while the clinical Projects study sex differences in central stress circuit activation and peripheral outputs of these circuits in human patients with IBS and IC, the two basic Projects study animal models of both disorders. State of the art technology ranging from molecular biological approaches to functional brain imaging techniques will be used to address the following specific aims in the four Projects: 1. Sex Differences in Central Stress Circuit Responsiveness in IBS and IC patients 2. Sex differences in the colonic responses to stress: Role of CRF pathways 3. Sex differences in neuroendocrine and immunologic responses in IBS 4. Sex differences in CRF, noradrenergic function and oxytocin in cats with IC. To facilitate the research, the Center has an Administrative Core and a Scientific Core (Neuroendocrine Measures) and will take advantage of existing NIH-funded core and service facilities on campus, including the CURE: Digestive Diseases Research Center, the UCLA Brain Mapping Center and the GCRC. The Center provides an optimal environment for cooperation and collaboration among its investigators, who already have had a major impact on the field individually. Thus, the synergy expected from the Center promises to have an even larger impact upon expanded research into a highly prevalent, but inadequately treated area of women's health. PERFORMANCESITE(S) (organization,city, state) The major site for the performance of the proposed work, including the Administrative Core, is the CURE:Digestive Diseases Research Center at Greater Los Angeles VA Healthcare Center campus, near the main UCLA campus in Los Angeles, California. Three of the P.Is and the Neuroendocrine Core Director have their offices and laboratories at CURE. The Neuroendocrine Core, The UCLA GCRC, the Divisional CRC, the UCLA Brain Mapping Center, and other support services are located on the main UCLA campus. The location of each member's laboratory, including the locations of the investigators at the Ohio State University and the Pittsburgh sites are indicated in each Project. Bruce Naliboff, PhD University of California LA, Dept. of Medicine Steve Berman, PhD University of California LA, Dept. of Medicine Edward Ornitz, MD University of California LA, Dept. of Medicine Million Mulugeta, DVM, PhD University of California LA, Dept. of Medicine Lixin Wang, PhD University of California, LA, Dept. of Medicine Vincent Wu, PhD University of California LA, Dept. of Medicine Lin Chang, MD University of California LA, Dept. of Medicine Peter Anton, MD University of California LA, Dept. of Medicine C.A. Tony Buffington, DVM, PhD Ohio State University, Dept. of Vet Clin Sci DisclosurePermissionStatement. Applicableto SBIR/STTROnly. See instructions. [] Yes KEYPERSONNEL. See instructions. Use continuationpages as needed to providethe requiredinformationin the format shownbelow. Startwith Principal Investigator.List all other key personnelin alphabeticalorder,last namefirst. Name Organization Role on Project Emeran Mayer, MD University of California, LA, Dept. of Medicine Center P,I. and Project(I) P.I. Yvette Tache, PhD University of CaIJfomia, LA, Dept. of Medicine Center Co-P.I. and Project(2) P.I. Investigator (Project 1) Investigator (Project 1) Investigator (Project 1) Investigator (Project 2) Investigator (Project 2) Investigator (Project 2) Project (3) P.I. Project (3) Co-P.I. Project (4) P.I. [] No " PHS 398 (Rev.05/01) Page _ {.) _'__} Form Page 2 . [unreadable] Key Personnel: Name Lori Birder, PhD Gordon Ohning, PhD Joe Reeve, PhD John Mazziotta, MD, PhD Shelley Taylor, PhD Jennifer Berman, MD Donald Guthrie, PhD Rita Valentino, PhD Paul Micevych, PhD Michael Irwin, MD Margaret Heitkemper, PhD, Pierre Baldi, PhD Gary Berntson, PhD Janet Amico, MD Janet Keast, PhD mPHS398(Rev. 05t01) Principal Investigator/PrograDmirector(Last,first, middle): Mayer, Emeran A. Organization Role on Project Pittsburgh University, Dept. of Medicine University of California Dept. of Medicine University of California Dept. of Medicine University of California LA, Dept. of Medicine University of California LA, Dept. of Psychology University of California LA, Dept. of Medicine University of California LA, Dept. of Psychiatry University of Pennsylvania, Dept. of Pediatrics University of California, LA, Dept. of Neurobiology University of California, LA, Dept. of Medicine RN, FAAN University of Washington, Seattle University of California, lrvine Ohio State University, Dept. of Psychology University of Pittsburgh, Dept. of Medicine Prince of Wales MRI, Australia Investigator (Project 4) Neuroendocrine Core, P.I. Neuroendocrine Core Co-P.I. Consultant (Project 1) Consultant (Project 1-4) Consultant (Project 1) Consultant (Projects 1-4) Consultant (Project 2, 4) Consultant (Project 2, 4) Consultant (Project 3) Consultant (Project 3) Consultant (Project 3) Consultant (Project 4) Consultant (Project 4) Consultant (Project 4) Page 0(J ['_ 3 FormPage2 [unreadable] PrincipInavl estigator/PDroirgercat(moLrasfti,rstm, iddle):Mayer, Emeran A. The nameof the principalinvestigatodprogramdirector must beprovidedat the topof each printedpageand each continuationpage. RESEARCH GRANT TABLE OF CONTENTS Page Numbers SECTION A. 1 Face Page .................................................................................................................................................. 2-3 Description,